The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Loss of mitogen-activated protein kinase kinase kinase 4 ( MEKK4) results in enhanced apoptosis and defective neural tube development.

Neural tube defects (NTDs) are prevalent human birth defects. Mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase ( JNK), are implicated in facilitating neural tube closure, yet upstream regulators remain to be identified. Here, we show that MAP kinase kinase kinase 4 ( MEKK4) is strongly expressed in the developing neuroepithelium. Mice deficient in MEKK4 develop highly penetrant NTDs that cannot be rescued by supplementation with folic acid or inositol. Unlike most mouse models of NTDs, MEKK4 mutant embryos display genetically co-segregated exencephaly and spina bifida, recapitulating the phenotypes observed in human patients. To identify downstream targets of MEKK4 during neural tube development, we examined the activity of MAP kinase kinase 4 ( MKK4), a signaling intermediate between MAP kinase kinase kinase and JNK/ p38. We found a significant reduction in MKK4 activity in MEKK4-deficient neuroepithelium at sites of neural tube closure. MAPK pathways are key regulators of cell apoptosis and proliferation. Analyses of the neuroepithelium in MEKK4-deficient embryos showed massively elevated apoptosis before and during neural tube closure, suggesting an antiapoptotic role for MEKK4 during development. In contrast, proliferation of MEKK4-deficient neuroepithelial cells appeared to be largely unaffected. MEKK4 therefore plays a critical role in regulating MKK4 activity and apoptotic cell death during neural tube development. Disruption of this signaling pathway may be clinically relevant to folate-resistant human NTDs.[1]


  1. Loss of mitogen-activated protein kinase kinase kinase 4 (MEKK4) results in enhanced apoptosis and defective neural tube development. Chi, H., Sarkisian, M.R., Rakic, P., Flavell, R.A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
WikiGenes - Universities